Schisandrin A alleviates mycophenolic acid-induced intestinal toxicity by regulating cell apoptosis and oxidative damage

Abstract

The gastrointestinal side effects of mycophenolic acid affect its efficacy in kidney transplant patients, which may be due to its toxicity to the intestinal epithelial mechanical barrier, including intestinal epithelial cell apoptosis and destruction of tight junctions. The toxicity mechanism of mycophenolic acid is related to oxidative stress-mediated, the activation of mitogen-activated protein kinases (MAPK). Schisandrin A (Sch A), one of the main active components of the Schisandra chinensis, can protect intestinal epithelial cells from deoxynivalenol-induced cytotoxicity and oxidative damage by antioxidant effects. The aim of this study was to investigate the protective effect and potential mechanism of Sch A on mycophenolic acid-induced damage in intestinal epithelial cell. The results showed that Sch A significantly reversed the mycophenolic acid-induced cell viability reduction, restored the expression of tight junction protein ZO-1, occludin, and reduced cell apoptosis. In addition, Sch A inhibited mycophenolic acid-mediated MAPK activation and reactive oxygen species (ROS) increase. Collectively, our study showed that Sch A protected intestinal epithelial cells from mycophenolic acid intestinal toxicity, at least in part, by reducing oxidative stress and inhibiting MAPK signaling pathway.

Keywords:

• Mycophenolic acid
• schisandrin A
• tight junction
• oxidative stress
• mitogen-activated protein kinases

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability statement

All data included in this study are available upon request by contacting the corresponding author.

Additional information

Funding

This study was supported by the Natural Science Foundation of Anhui Province Education Department [KJ2019A0247], the First Affiliated Hospital of Anhui Medical University Doctoral Research Funds [BSKY2019009].